title: PDGF alpha-receptor mediated cellular responses are not dependent on Src family kinases in endothelial cells.
abstract: Two novel autophosphorylation sites in the juxtamembrane region of the PDGF alpha-receptor, Tyr-572 and Tyr-574, were identified. A Y572/574F mutant PDGF (alpha)-receptor was generated and stably expressed in porcine aortic endothelial cells. In contrast to the wild-type receptor, the mutant receptor was unable to associate with or activate Src family tyrosine kinases. Tyrosine phosphorylated synthetic peptides representing the juxtamembrane sequence of the receptor dose-dependently inhibited the binding of Src family tyrosine kinases to the autophosphorylated PDGF alpha-receptor. The mutant receptor showed similar PDGF-induced kinase activity and ability to mediate mitogenicity, actin reorganization and chemotaxis as the wild-type receptor. Thus activation of Src family kinases by the PDGF alpha-receptor is not essential for PDGF-induced mitogenicity or actin reorganization.
authors.affiliation: Ludwig Institute for Cancer Research, Box 595, Biomedical Center, S-751 24 Uppsala, Sweden.
authors.forename: R
authors.initials: R
authors.lastname: Hooshmand-Rad
authors.forename: K
authors.initials: K
authors.lastname: Yokote
authors.forename: C H
authors.initials: CH
authors.lastname: Heldin
authors.forename: L
authors.initials: L
authors.lastname: Claesson-Welsh
mesh_terms: D000199:Actins / Q000648:ultrastructure; D000595:Amino Acid Sequence; D002460:Cell Line; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology*; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics / Q000502:physiology*; D013936:Thymidine / Q000378:metabolism; D014316:Tritium; D014443:Tyrosine; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D000199:Actins; D014316:Tritium; D014443:Tyrosine; D017479:Receptors, Platelet-Derived Growth Factor; D019061:src-Family Kinases; D013936:Thymidine